Antiseptic detergent compositions



United States Patent 3,256,201 ANTIISEPTIC DETERGENT COMPOSITIONS Darwin R. Noel and Robert E. Casely, Chicago, 111., assignors to Armour and Company, Chicago, Ill., a corporation of Delaware No Drawing. Filed July 23, 1962, Ser. No. 211,837 4 Claims. (Cl. 252-107) This application is a continuation-in-part of our copending application Serial No. 537,057, filed September 27, 1955, now Patent No. 3,081,266.

This invention relates to antiseptic compositions having a synergistic effect. In one of its aspects, this invention relates to improved germicidal cleansing compositions containing as their essential active germicidal ingredients a synergistic combination of an unalkylated halogenated bis-phenol and an alkylated halogenated bis-phenol in which the alkyl groups contain from 1 to 4 carbon atoms.

The popularity of germicidal cleansing compositions for laundry and toilet use has increased tremendously over the past few years. In fact, it has been estimated that 40% of the bar soap sales now are of products containing a germicidal agent, and this percentage is steadily increasing. There are a number of germicidal agents currently in use, but the halogenated bis-phenols appear to be the most widely accepted because of their activity, compatability, and commercial availability. One of the desirable compounds of this class is 2,2- dihydroxy 3,5,6,3',5,6' hexachlorodiphenyl methane, commonly known as hexachlor-ophene, which is now in widespread commercial use. The action of halogenated bis-phenols such as hexachlorophene when incorporated in soap, the proportions required, and other pertinent information is set out more fully in US. Patent No. 2,535,077 to Kunz et al.

There are certain inherent disadvantages to the use of halogenated bis-phenols. For example, they are photosensitive and tend to cause discoloration in the finished product on exposure to light. Also, they are somewhat toxic and present a potential hazard to domestic animals which are prone to eat things, even soap. Therefore, it would be desirable to diminish these disadvantage without adversely affecting the germicidal actvity of the halogenated bis-phenol. Viewed in a different light, it would also be worth while if the disadvantages could be maintained at the present level and the germicidal activity of the halogenated bis-phenol increased. We have discovered that these objects can be accomplished through through the production of the synergic effect.

In accordance with the present invention, the germicidal activity of unalkylated halogenated bis-phenol is enhanced, synergized or potentiated by the incorporation therewith of an alkylated halogenated bis-phenol in which the alkyl groups contain from 1 to 4 carbon atoms. The products of this invention, therefore, are antiseptic compositions containing as their essential active ingredient a synergistic combination of an unalkylated halogenated bis-phenol and an alkylated halogenated bis-phenol in which the alkyl groups contain from 1 to 4 carbon atoms.

The unalkylated halogenated bis-phenol used in accordance with the present invention can be represented by the following structural formula:

wherein X represents a halogen such as chlorine or bro- 7 mine, n represents an integer of from 1 to 3, and R represents a divalent alkylene radical having 1 to 4 carbon atoms such as -CH CH CH CH(CH -C(CH3)2-, CH2CH2CH2 and the llk. The pre- 5-tetrachlorodiphenyl methane, and 2,2'-dihydroxy-5,5'-

dibromodiphenyl methane.

The alkylated halogenated bis-phenols used in conjunction with the unalkylated halogenated bis-phenols in the present invention can be any suitable bis-phenol composition characterized by the presence of short-chain alkyl groups in the aromatic rings. These substances can be represented according to their chemical structure as follows:

HO OH preferred compounds are symmetrical in structural c0n-' figuration. Specific examples of the alkylated halogenated bis-phenols include 2,2'-dihydroxy-3,3'-dimethyl-5,5'-dichlorodiphenyl sulfide, 2,2'-dihydroxy-3 ,3 -dimethyl-5 ,5 -dichlorodiphenyl trichloroethane, 2,2'-methylene-bis 4-chloro-6-isopr-opyl-phenol) 2,2-methylene-bis 6sec-butyl-4-chlorophenol) 2,2-ethylidene-bis 4-chloro-6-isopropylphenol) 2,2'-ethylidene-bis 6sec-butyl-4-chlorophenol) 2,2'-isopropylidene-bis 4-chloro-6-isopropylphenol) and 2,2-isopropylidene-bis(6-sec-butyl-4-chlorophenol) It has been found that when the unalkylated halogenated bis-phenols and the alkylated halogenated bisphenols, as illustrated above, are used together in an antiseptic composition, a germicidal effect is achieved which is greater than the mere total of the individual effects of the individual ingredients. This has importance in cases where the activity of the unalkylated halogenated bis-phenol is desired to be increased without employing higher concentrations, and in other cases it assumes an even greater importance from an economic standpoint, since the presence of the alkylated halogenated bis-phenol enables a substantial reduction in the concentration of the germicidal agent while at the same time retaining the desired level of germicidal activity.

What the actual mechanism of the potentiating or synergistic effect might be, we are unable to explain. The invention relates to the synergistic cooperation of these two types of compounds when used in minor proportions in an antiseptic composition, and especially an antiseptic detergent composition, and the discovery that this synergistic phenomenon occurs even at pH conditions existing in soap and detergent formulations provides one of the important phases of the present invention.

Relatively small amounts of the unalkylated halogenated bis-phenol and the alkylated halogenated bisphenol are sufficient for the increased germicidal effect of the present invention. Satisfactory results are obtained when the combined weight of the two types of bis-phenols are from 1 to 3% of the total weight of the composition.

3 The objects of the invention are achieved when the weight of the unalkylated halogenated bis-phenol is about 0.1% to 3% and the alkylated halogenated bis-phenol is about 3% to 0.1% by weight based upon the detergent or soap.

of dodecyl, hexadecyl, and octadecyl sulfate; the sulfonated fatty acid amides such as the sodium or potassium salts of the oleic acids of methyl taurine; and the sulfoof Action of Antibiotic synergism and Antagonism, Department of Microbiology, University of California School of Medicine. In the place of the plate counts used in the published method, the end point of chemical The preferred weight is a concentration of about 0.25% activity in the present method was taken as that point to 1.75% of the unalkylated halogenated bis-phenol and at which no growth was apparent in the broth tubes. about 1.75% to about 0.25% of the alkylated halogenated The minimum effective dose of 2,2 dihydroxybis-phenol, and an excellent product is one containing a 3,5,6,3,5,6-hexachlorodiphenyl methane (hexachlorodetergent soap and about 1% of each of the unalkylated phene), 2,2' dihydroxy 3,3 dimethyli hl r i halogenated bis-phenol and the alkylated halogenated bisp nyl Sulfide, d y r vim v1- iphenol. It will be understood that even concentrations p nyl trichloroethane were first determined by below the ranges just set out will provide some degree of diluting the prepared StOCk solutions of the test chemicals germicidal effect and that substantially higher concenin a series of tubes containing 1 1111- Of nut e broth trations than those given will provide satisfactory results, c lture medium. Each successive tube in the series conalthough there are certain practical considerations, such is mined e te t chemicals at /2 the concentration of the as the cost of the bis-phenol and a certain impairment in previous tube. 0.1 ml. of a 1-10 dilution of a 24 hour detergent properties, which limit the desirability of includbroth Culture the test Organisms FY 8 ing greater amounts of the ge-rmieide in the soap, aureus was then added to each'tube 0f the broth tubes in The term soap refers to the water-soluble ammonium, the series. The period Of incubation for all tubes was metallic, organic base salts of variousfatty acids, which 8 ours at a temperature of 37 C. The end point or are chiefly laurie, oleie, stearie, and palmitie acids As minimum effective ClOSe Of chemical was taken as that used in this specification and claims, the term is intended Point at which no growth Was pp in t113 highest to cover all products in which soap is a major constituent, dilution of the chemical in the broth tube. for example, bar, flake, powdered, soft and liquid soaps; After determining the minimum fiftCCtiVe doses of the shaving creams, toothpastes, cleansing creams, etc. individual test chemicals, each of the other two test chemi- The invention also contemplates the use of anionic-type Gals Were Combined With Phene in a series of synthetic detergents in place of the soap, The anionicbroth tubes at a concentration in bIOth at sub-inhibitory type synthetics suitable for use in the invention can be and near sub-inhibitory lVlS Of all chemicals. There described as those deter-gents having pronounced cleansing were tWO Series Of 16 tllbfis each, each tube Containing power and including in their .moleonlar structure an alkyl hexachlorophene and the individual tESt chemical in EL radical ontaining from 6 to carbon atoms ,and a uidifferent ratio. Inoculation the test organism M- fonic acid or sulfuric acid ester radical. Either organic py v ablleus Was ad in ach tube in the series base, ammonium, sodium or potassium salts of the a by adding t0 321Gb tube 0.1 ml. Of a ll0 ClillltiOIl Of a. ionic type detergents can be used The main types of 24 hour broth C ltLlZ '6 Of llllfi organism. The incubation 4 detergents falling within this category are the alkyl-aryl P r was 43 hours at a temperature of The suifonates, h as di or potassium d d i benzene determination of synergistic activity was made in the tube sulfonate, sodium or potassium octadecyl benzene sulfotubes having the IOWeSt b-in ibitory oncentration mate and sodium or potassium voctyl naphthalene ulfo Of both hexachlorophene and the individual test chemical mate; the alkyl sulfates such as sodium or potassium salts Showing pp g Wth of the test organism.

The results of these tests setting forth the minimum effective dose in micrograms per milliliter is set forth in Table I.

TABLE I Test Chemicals M.E.D. Growth Combined gJml. After 48 hrs. Eilect phenyl methane (A). 2,2-dihydroxy-3,3'-dimethyl-5,5-dichl0ro- O. 5 0

diphenyl sulfide (B). 2,2-dihydroxy-3,3-dimethyl-5,5-dich1or0- 0. 5 0

diphenyl trichloroethane (C). (A) plus (B) 0. 05+0. 25 0 synergism. (A) plus 0 0. 054-0. 25 0 D0,

nated monoglycerides such as the-mono-coconut oil fatty Example 11 acid ester of 1,2-hydroxy propane-3-sodium sulfonate.

The unalkylated halogenated bis-phenol and the alkylated halogenated bis-phenol can be added to the soap or the detergent by any suitable method which results in a uniform distribution of the additives throughout the Antiseptic detergent compositions exemplary of the present invention were prepared by intimately mixing the ingredients listed in Table II to form a composite containing 2% by Weight active ingredient:

entire mass. A highly satisfactory dispersion method of TABLE II carrying out the additional step is described more fully in the copending application Serial No. 263,302, filed Composition A l B l o D E December 26, 1951, now abandoned.

Specific examples illustrating the invention are as folggli fig gggf g g gfigfi 98 98 98 98 98 lows: i e a h ordi hnbiMethane 2 1 1 1 y rox ,3 -dimeth l-5,5- 7 Example I 2 gighilorgdip l egnglgulfidelg 2 1 7 1 y roxy imethy -5,5- The procedure employed for determining the minimum dlchlomdlphenyl mchloroethane 2 1 effective dose (M.E.D) represents a variation of a method Pubhshed 111 the curnal 0f Gineral f y, Volume Aliquots of each of the above described compositions 10, No. 2, April 1954, on Observat1ons on the Mode containing 2% by weight active ingredient were added 6 to nutrient agar medium so as to give in each instance TABLE III a concentration of 0.25 parts per million of active ingredient in agar. The agar in each case was then Composition A B o D E poured into a petri dish, allowed to harden and then streaked with a 24-hour old broth culture of M. pyogenes 5 period incubation, hours 48 48 48 48 48 var. aureus diluted 1-10. The incubation in each case Amount Ofgrowth was at 37 C. The degree of growth after 48 hours is noted in Table III, as follows: Legend:

1+ =Very slight growth (100 colonies present). TABLE III 2+=Light to moderate growth (IOU-1,000 colonies present).

3+=Normal heavy growth (over 1,000 colonies present). Composition l A l C D l n While this invention has been described and exempli- Period oimcubatiom" 48 48 48 48 fied in terms of its preferred embodiments, those skilled Amount ofgrowth 3+ 3+ 3+ 1+ in the art will appreciate that Variations can be made without departing from the spirit and scope of the ing rowth vention.

2+=L ate growth. 1. An antiseptic detergent composition comprising a 3+=Nrmalheavy growth water soluble soap and a minor weight proportion in re- ExamPleIH spect to the soap of an antiseptic combination, having a The Same microbiological .toohniquos set f th i synergistic eifect, consisting of from about 0.1% to about ample I were employed except that a neutral white soap y Welght based P ihe -P 0f i Y Y- (Ivory) was used instead of a broth; the test organism 5 'i 'i P y1 a from a u was S. aureus and the test chemicals were employed in 30% to about 01% y wel'ght based p the p of a 1% total active level basis the soap; and the test results 25 y Y- i y di-chlol'odiphenyl were as follows: chloroet'hane.

TABLE I M.E.D., Growth Combined Test Chemicals g.lrnl. afitlerrs 48 Eliect phenyl methane (A) 0.2 0 2,2-dihydroxy-3,3-dimethyl 5,5 -dichlorodiphenyl sulfide (B) 0. 5 0 2,2-dihydroxy-3,3-dimethyl-5,5-dichlorodiphenyl trichloroethane (G) 0. 5 0 (A).plus (B) 0. 05-1-0. 25 0 synergism. (A) plus 0 0. 05+0. 25 0 Do.

As indicated in Table I of Example I and in Table I 2. An antiseptic detergent composition comprising a of Example III, the proportions of about 5 parts of 2,2- Water soluble soap and about 2% by weight based upon dihydroxy-3,3'-dimethyl-5,5-dichlorodiphenyl trichlorothe soap of a mixture of equal parts by weight of 2,2- ethane to 1 part by weight of 2,2'-dihydroxy3,5,6,3,5, dihydroxy-3,5,6,3',5',6-hexachlorodiphenyl methane and 6'-hexachlorodi-phenyl methane demonstrate synergism. 4.5 hydr0Xy-3,3'-dirnethy1-5,5'-dichlorodiphenyl tri- Antiseptic detergent compositions were prepared by chlomel-"hane; intimately mixing ingredient listed in Table 11 below to x AH antlseptw detergent composltlor} comprlsmg a form a composite containing 1% by Weight of active water soluble soap and about 1-2% 'by weight based upon ingmdient: the soap of a mixture of equal parts by weight of 2,2 -dr- 50 hydroxy-3,5,6,3',5',6'-hexachlorodrphenyl methane and 2,2-dihydroxy-3,3 -dimethyl-5,S '-dichlorodiphenyl trichlo- TABLE H roethane.

4. An antiseptic composition consisting essentially of a cmposmm A B l C D E synergistic combination of from about 0.1% to about 3.0% by weight of 2,2'-dihydroxy-3,5,6,3',5,6'-hexachlogfitf i g f g g g g gi gi gfggg ifg g 99 99 99 99 99 rodiphenyl methane and from about 3.0% to about 0.1% qipr1eny1meirie1... 0.5 0.5 by weight of 2,2'dihydroxy-3,3-dimethyl-5,5-dich1oroi ggi gggggfifi iiiiigf ffiff i 5 diphenyl trichloroethane, and wherein the ratio of the said 2,2-dihydroxy-(i-dimethyl-5,5-dihexachlorodiphenyl methane to the said trichloroethane chlomdlphenyl mchlomethane 1 5 is in the range of about 1 to 1 to about 1 to 5,

References Cited by the Examiner UNITED STATES PATENTS Alrquots of each of thaabove-descnbed compositions 2,535,077 12/1950 Kunz et a1 252 1O7 containing 1% by weight active ingredient were added 2,671,813 3/1954 S-tofieL to a nutrrent iagar medlum so as to g ve 1n eaoh instance 2 14 5 11 195 Wenneis et a1 a concentration of 0.25 parts per million of aot1ve 1n- 0 4 097 4/1963 Roller et 167 30 gredient in agar; the agar in each instance was then 3,084,122 4/1963 Cypert et a1 252 &55 poured into a Petri dish, allowed to harden, and then 3,102,070 8/1963 Riley et al 167--30 streaked with a 24-hour broth culture of M. pyogenes var. aureus diluted 1-10; the incubation was in each case at 37 C.; the degree of growth after 48 hours was noted and is set out in Table III as follows:

JULIUS GREENWALD, Primary Examiner.

ALBERT T. MEYERS, Examiner.

W. E. SCHULZ, Assistant Examiner. 

1. AN ANTISEPTIC DETERGENT COMPOSITION COMPRISING A WATER SOLUBLE SOAP AND A MINOR WEIGHT PROPORTION IN RESPECT TO THE SOAP OF AN ANTISEPTIC COMBINATION, HAVING A SYNERGISTIC EFFECT, CONSISTING OF FROM ABOUT 0.1% TO ABOUT 3.0% BY WEIGHT BASED UPON THE SOAP OF 2,2''-DIHYDROXY3,5,6,3'',5'',6''-HEXACHLORODIPHENYL METHANE AND FROM ABOUT 3.0% TO ABOUT 0.1% BY WEIGHT BASED UPON THE SOAP OF 2,2''-DIHYDROXY-3,3''-DIMETHYL-5,5''-DICHLORODIPHENYL TRICHLOROETHANE. 